A commonly use method of measuring the isotopic ratio of components of a gaseous sample is that of comparing the gaseous sample in a measurement cell, with a reference gas measured under similar conditions. Such a method, using mass spectrometric measurements as the comparison criterion, has been described in Chapter 16 of the book entitled “Tracers in Metabolic Research—Radio-isotopes and Stable Isotope/Mass Spectrometer Methods” by Robert R. Wolfe, Alan R. Liss Inc., New York (1984). The disclosures of that publication and of all other publications mentioned in this specification, and the disclosures of all documents cited in those publications, are hereby incorporated by reference.
Infra-red gas absorption can also be used as a means of analyzing the content of gaseous mixtures, since each gas has its own absorption characteristics, which differentiates it from other gases. The non-dispersive absorption of light in a gas is governed by the well-known Lambert-Beer law, which states that:I=Io.exp {−[c]..d}
where I is the intensity of the transmitted light,                Io is the intensity of the incident light,        [c] is the molar concentration of the gas absorbing the light,        d is the path length of the light in the gas, and         is the absorption coefficient per unit length, also known as the extinction coefficient.The molar concentration of the gas is directly proportional to its partial pressure, for a given volume of gas at a given temperature. It would therefore seem that a simple measurement of the transmission of light through a known length of the gas to be analyzed would be sufficient to determine its partial pressure or concentration. This is the basis of the technique known as non-dispersive infra-red spectroscopy, which is a primary methods in use today for gas analysis, and a large volume of reference work is available on the subject. Isotopic differentiation is becoming an increasingly important analytical tool, especially in such fields as breath tests for medical diagnostic testing. Sensitive NDIR spectrometers, capable of measuring changes in rare isotopic concentrations, are thus becoming important in the field of medical instrumentation, and others.        
The absorption phenomenon used for performing such NDIR spectroscopy, as it is known, is the absorption of light energy by gaseous molecules undergoing transitions between rotational-vibrational levels. The energy levels involved place these transitions in the infra-red region of the spectra. As an example, the absorption spectra of CO2 molecules is centered in the 4.2 to 4.45 μm region, and in general, black body infra-red sources have been used for performing such measurements. Such black body sourced spectrometers have difficulty in differentiating between various isotopes of gases, since there is only an extremely small shift in absorbed wavelength when an atom in a gas is replaced by a chemically identical isotopic atom. Since isotopic differentiation is becoming an increasingly important analytical tool, especially in such fields as breath tests in medical diagnostic testing, sensitive NDIR spectrometers capable of measuring changes in rare isotopic concentrations, are becoming important in the field of medical instrumentation and others.
In order to define the exact wavelength of the measurement, a means for discriminating between the various isotopes of the gas sample is needed. If a black body is used as the source of radiation, it is necessary to use some form of sophisticated narrow band filter, which would transmit only those regions where no spectral overlap is possible. Because of the inherent continuous nature of the black body spectrum, as opposed to the discrete nature of the absorption spectrum of the isotopic gas mixture, by using only those remaining spectral regions makes this method insensitive for isotope discrimination, and requires the use of very long optical absorption paths to achieve adequate sensitivity. In addition, black bodies cannot be modulated at frequencies which give useful detection advantages and so have to have modulation applied to their radiation by external means.
Even if a wavelength sensitive detector, such as an acousto-optic detector, is used with the black body to define a narrow wavelength region where the absorption measurement takes place, significant overlap of the various isotope spectral absorption lines dictates the use of complex correction and compensation algorithms, as shown for instance in European Patent Application No. EP 0 584 897 A1 to W. Fabinsky et al.
As an alternative technology, in U.S. Pat. No. 4,755,675 there is described a gas analyzer using a wavelength specific infra-red lamp source, based on a gas-filled discharge tube, which emits the characteristic spectral lines of the gas filling the lamp. By selecting the filling gas, it is possible to perform analysis of gas mixtures containing the gas used for the lamp fill. The authors even suggest that, being able to make use of such specific IR sources, an IR analyzer according to their invention would be capable of identifying and measuring the concentration of isotopically substituted “marker” molecules. However, the patent does not provide any explanation of how this can be performed in practice. These lamps have been successfully used in capnography applications. However, for use in gas isotopic measurements, which require sensitivity and selectivity at least one order of magnitude higher than for capnographic measurements, the measurement and application techniques previously reported are totally inadequate.
Part of the complexity of gas isotope analysis arises because the Lambert-Beer law is only an approximation. In particular, the absorption coefficient , is not a constant at all, but is dependent on a wide range of environmental factors, such as the analyzed gas pressure and temperature, the ambient humidity, the spectral characteristics resulting from the operating conditions of the radiating source, gas carriers in the analyzed gas, and short and long term changes in the radiating source spectral characteristics. Many of the NDIR spectrometers described in the prior art have attempted to overcome this problem by using closely controlled environmental conditions, predetermined correction factors, or frequent, complex calibration techniques, or a combination of all three. Some examples of such prior art analyzers include the analyzer described by W. Fabinsky et al. in European Patent No. EP 0 584 897 A1, that described by R. Grisar et al. in U.S. Pat. No. 5,146,294, and that described by Y. Kubo et al. in PCT Patent Application No. WO 97/14029.
In U.S. Pat. No. 5,140,993, to A. R. Opekun and P. D. Klein, is described a device for collecting a breath sample. This breath sample collection bag is operative to collect breaths exhaled by a patient, until sufficient have been collected for transfer to the analysis instrument. The breaths are inputted into the bag by means of a mouthpiece into which the patient blows, and the entry of the breath is controlled either by a check valve, that permits gas flow only towards the inside of the bag, or by a stop-cock valve, manually operated either by the patient himself or by an attending medical assistant. No criteria are given for the opening of the check valve, other than its function to permit gas flow only towards the inside of the bag, as for the stop-cock valve. This breath sample collection bag thus acts as a very simple form of collection reservoir, performing simple breath averaging, with the limited advantages which this offers.
To the best of applicants' knowledge, none of the prior art instruments attach importance to the fact that if parts of the breath other than from the plateau are collected for analysis, there may be serious implications for the measurement accuracy.
All of the above described prior art analyzers appear to be complex, costly analytical instruments, which in most cases are also difficult to operate because of the rigorous and frequent calibration procedures required. To the best of the inventors' knowledge, no prior art gas analyzers exist which provide sufficient sensitivity and selectivity that enable them to be used for tests such as medical isotopic breath testing, and yet which are sufficiently compact, rugged and low cost, not requiring stable laboratory environments to enable them to become accepted for widespread use in the medical community.
The disclosures of all publications mentioned in this section and in the other sections of the specification, and the disclosures of all documents cited in the above publications, are hereby incorporated by reference.